title: The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile.
abstract: BACKGROUND
  Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints.
  
  
  METHODS
  Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation.
  
  
  RESULTS
  By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated.
  
  
  CONCLUSIONS
  This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.
authors.affiliation: Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Republic of Singapore. dmskol@nccs.com.sg
authors.forename: Oi Lian
authors.initials: OL
authors.lastname: Kon
authors.forename: Tai-Tung
authors.initials: TT
authors.lastname: Yip
authors.forename: Meng Fatt
authors.initials: MF
authors.lastname: Ho
authors.forename: Weng Hoong
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authors.lastname: Chan
authors.forename: Wai Keong
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authors.lastname: Wong
authors.forename: Soo Yong
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authors.lastname: Tan
authors.forename: Wai Har
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authors.lastname: Ng
authors.forename: Siok Yuen
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authors.lastname: Kam
authors.forename: Alvin Kh
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authors.lastname: Eng
authors.forename: Patrick
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authors.lastname: Ho
authors.forename: Rosa
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authors.lastname: Viner
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authors.lastname: Ong
authors.forename: M Priyanthi
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authors.lastname: Kumarasinghe